Highlights • A non-coding variant on chromosome 6 associates with five vascular diseases • Histone acetylation shows a vascular-specific regulatory element at the causal SNP • Genome editing at the SNP demonstrates distal regulatory effect on endothelin-1 • Endothelin-1 signaling in blood vessels may explain pattern of vascular disease risk Summary Genome-wide association studies (GWASs) implicate the PHACTR1 locus (6p24) in risk for five vascular diseases, including coronary artery disease,...